Age-related physical and cognitive decline may be ameliorated by consuming functional foods. d-Allose, reported to have multiple health benefits, may temper aging phenotypes, particularly brain function. We investigated whether d-allose supplementation improves cognitive function.
View Article and Find Full Text PDFAlthough reactive oxygen species (ROS) are known to have harmful effects in organisms, recent studies have demonstrated expression of ROS synthases at various parts of the organisms and the controlled ROS generation, suggesting possible involvement of ROS signaling in physiological events of individuals. However, physiological roles of ROS in the CNS, including functional roles in higher brain functions or neuronal activity-dependent ROS production, remain to be elucidated. Here, we demonstrated involvement of ROS - 8-NO-cGMP signaling in motor learning and synaptic plasticity in the cerebellum.
View Article and Find Full Text PDFThe nucleotide second messenger 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP) mediate fundamental functions of the brain, including learning and memory. Phosphodiesterase 3 (PDE3) can hydrolyze both cAMP and cGMP and appears to be involved in the regulation of their contents in cells. We previously demonstrated that long-term administration of cilostazol, a PDE3 inhibitor, maintained good memory performance in aging mice.
View Article and Find Full Text PDFD-Allose, a C3 epimer of D-glucose, has potential to improve human health as a functional food. However, its effect on the intestinal environment remains unknown. Aged humans progressively express changes in the gut, some of which deleteriously affect gastrointestinal health.
View Article and Find Full Text PDFBackground Metabolic syndrome is characterized by insulin resistance, which impairs intracellular signaling pathways and endothelial NO bioactivity, leading to cardiovascular complications. Extracellular signal-regulated kinase (ERK) is a major component of insulin signaling cascades that can be activated by many vasoactive peptides, hormones, and cytokines that are elevated in metabolic syndrome. The aim of this study was to clarify the role of endothelial ERK2 in vivo on NO bioactivity and insulin resistance in a mouse model of metabolic syndrome.
View Article and Find Full Text PDFWe previously demonstrated the marked hepatosteatosis and endothelial dysfunction in hepatocyte-specific ERK2 knockout mice (LE2KO) with a high-fat/high-sucrose diet (HFHSD), but detailed metabolic changes and the characteristics in insulin-sensitive organs were not tested. This study aimed to characterize metabolic remodeling with changes in insulin-sensitive organs, which could induce endothelial dysfunction in HFHSD-LE2KO. The serum glucose and fatty acid (FA) were modestly higher in HFHSD-LE2KO than HFHSD-Control.
View Article and Find Full Text PDFObesity induces severe disorders such as type 2 diabetes and cardiovascular events, and the number of people with obesity is increasing all over the world. Furthermore, it is possible that obesity increases the risk of cognitive dysfunction via the acceleration of oxidative damage. Tocotrienols, which are part of the vitamin E family, have antioxidant and anti-obesity effects.
View Article and Find Full Text PDFTracheal stenosis is a refractory and recurrent disease induced by excessive cell proliferation within the restricted tracheal space. We investigated the role of extracellular signal-regulated kinase (ERK), which mediates a broad range of intracellular signal transduction processes in tracheal stenosis and the therapeutic effect of the MEK inhibitor which is the upstream kinase of ERK. We histologically analyzed cauterized tracheas to evaluate stenosis using a tracheal stenosis mouse model.
View Article and Find Full Text PDFAging is characterized generally by progressive and overall physiological decline of functions and is observed in all animals. A long line of evidence has established the laboratory mouse as the prime model of human aging. However, relatively little is known about the detailed behavioral and functional changes that occur across their lifespan, and how this maps onto the phenotype of human aging.
View Article and Find Full Text PDFBackground: Itch is a common cutaneous symptom in a variety of dermatological diseases, but detailed neuropathological mechanisms remain to be fully elucidated. This study aimed to assess in vivo ERK2 functions in the nervous system for itch responses.
Methods: We generated conditional knockout mice deficient in ERK2 of the central nervous system (CNS) or peripheral nervous system (PNS), respectively, and assessed chemical and mechanical itch responses in vivo.
Nervous systems are designed to become extra sensitive to afferent nociceptive stimuli under certain circumstances such as inflammation and nerve injury. How pain hypersensitivity comes about is key issue in the field since it ultimately results in chronic pain. Central sensitization represents enhanced pain sensitivity due to increased neural signaling within the central nervous system (CNS).
View Article and Find Full Text PDFThe mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24-h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circadian phase advances involves a nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway, increasing the expression of Period () genes. Effectors downstream of PKG remain unknown.
View Article and Find Full Text PDFICER (inducible cAMP early repressor) isoforms are transcriptional repressors encoded by the Crem (cAMP responsive element modulator) gene. They were linked to the regulation of a multitude of cellular processes and pathophysiological mechanisms. Here, we show for the first time that two independent induction patterns for CREM repressor isoforms exist in the heart, namely for ICER and smICER (small ICER), which are induced in response to β-adrenergic stimulation in a transient- and saturation-like manner, respectively.
View Article and Find Full Text PDFThe AP-1 transcription factor JunB plays crucial roles in multiple biological processes, including placental formation and bone homeostasis. We recently reported that JunB is essential for development of Th17 cells, and thus Junb-deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4 T cells under other inflammatory disease conditions is unknown.
View Article and Find Full Text PDFChloramphenicol (Cm) is a broad-spectrum classic antibiotic active against prokaryotic organisms. However, Cm has severe side effects in eukaryotes of which the cause remains unknown. The plant pathogenic fungus Magnaporthe oryzae, which causes rice blast, forms an appressorium to infect the host cell via single-cell differentiation.
View Article and Find Full Text PDFBiochem Biophys Res Commun
March 2019
We previously reported that 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins through S-guanylation. S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is a part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that regulates exocytosis. However, the biological relevance of 8-nitro-cGMP in the nervous system remains unclear.
View Article and Find Full Text PDFBackground: Vitamin C (l-ascorbic acid, VC) and vitamin E (α-tocopherol, VE) play important physiological roles as endogenous antioxidants in many tissues and organs. However, their roles in the brain remain entirely elusive. We established senescence marker protein 30 (SMP30)/α-tocopherol transfer protein (αTTP) double knockout (DKO) mice as a novel VC and VE double-deficiency model and examined the effect of VC and VE double-deficiency on brain functions.
View Article and Find Full Text PDFMany tumors evolve sophisticated strategies to evade the immune system, and these represent major obstacles for efficient antitumor immune responses. Here we explored a molecular mechanism of metabolic communication deployed by highly glycolytic tumors for immunoevasion. In contrast to colon adenocarcinomas, melanomas showed comparatively high glycolytic activity, which resulted in high acidification of the tumor microenvironment.
View Article and Find Full Text PDFAs the population of older individuals grows worldwide, researchers have increasingly focused their attention on identifying key molecular targets of age-related cognitive impairments, with the aim of developing possible therapeutic interventions. Two such molecules are the intracellular cyclic nucleotides, cAMP and cGMP. These second messengers mediate fundamental aspects of brain function relevant to memory, learning, and cognitive function.
View Article and Find Full Text PDFβ-Amyloid (Aβ) plays an important role in the early pathogenesis of Alzheimer's disease (AD). In vitro studies have demonstrated that Aβ oligomers induce hippocampal and neocortical neuronal death. However the neurotoxic mechanisms by which soluble Aβ oligomers cause neuronal damage and death remain to be fully elucidated.
View Article and Find Full Text PDFNiemann-Pick type C disease (NP-C) is a fatal neurodegenerative disorder caused by a deficiency of NPC1 gene function, which leads to severe neuroinflammation such as astrogliosis. While reports demonstrating neuroinflammation are prevalent in NP-C, information about the onset and progression of cerebellar astrogliosis in this disorder is lacking. Using gene targeting, we generated vascular endothelial growth factor (VEGF) conditional null mutant mice.
View Article and Find Full Text PDF